Although a variety of objective clinical and laboratory abnormalities have been reported in Chronic Fatigue Syndrome (CFS), none is either sensitive or specific for all patients fulfilling the current criteria for case definition. Acute exercise testing likewise yields a spectrum of findings. Remarkably consistent, however, are the patients' complaints that minor amounts of exertion lead to exacerbation of symptoms for periods of days. Knowing the basis for this phenomena would contribute to understanding the pathogenesis of CFS, and might also provide insight into the nature of subjective fatigue in other disease states. In normal subjects, cardiac, vascular, ventilatory and metabolic adjustments to exercise are tightly controlled to maintain homeostasis of critical functions. While high intensity exercise is accompanied by an acute stress response, including changes in markers of non-specific immune activation, homeostasis must nevertheless be reestablished when exercise ends. Given the interactions between the endocrine, immunologic, and autonomic nervous system responses activated during exercise, it is hypothesized that one of more of these is poorly regulated in patients with CFS. In support of this premise, proportions of CFS patients in various studies are reported to have: abnormal cardiocirculatory responses to exercise, decreased cortisol production, and increased levels of cytokines. Preliminary studies of acute responses to exercise in CFS patients demonstrated abnormalities suggestive of altered cardiovascular responses suggestive of either impaired vasoregulation, altered muscle bioenergetics, or perhaps severe deconditioning. These data were used to design protocols to investigate exercise intolerance in chronic fatigue syndrome. Specific aims include: 1) identifying clinical features predicting decreased exercise capacity in CFS, 2) assessing the dynamic control of cardiovascular response to submaximal exercise in CFS patients with abnormal exercise capacity, 3) determining muscular work efficiency in CFS patients, and 4) testing the hypothesis that exaggerated or prolonged humoral or inflammatory responses accompany acute exercise in patients with CFS, delaying the return to homeostasis.